Drug delivery device

ABSTRACT

There is described a patch pump comprising a cartridge, a power source, a pump system, a drug delivery device and a control system configured to operate in particular the pump system and the drug delivery device. The pump system comprises, on the one hand, a pump having a pump housing containing a pump piston and a valve piston and, on the other hand, a pump drive comprising a piston motor and a valve motor for driving the pump piston and the valve piston independently from each other through a first and a second transmission. The drug delivery device comprises a transdermal delivery system having a needle actuation mechanism configured for transdermal insertion of a cannula.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application is a national stage entry of International (PCT)Patent Application Number PCT/EP2018/052179, filed Jan. 29, 2018, whichin turn claims priority to European Patent Application No. 17153997.6,filed Jan. 31, 2017, the subject matter of which are expresslyincorporated herein by reference.

TECHNICAL FIELD

The present invention relates to a drug delivery device for transdermaldelivering a medicament. The drug delivery device may in particular bein the form of a patch pump for drug delivery incorporating a pumpsystem and a transdermal delivery system.

DESCRIPTION OF RELATED ART

The regular trans-dermal administration of doses of a medicament isnecessary in the control or therapy of many conditions, such asdiabetes, growth hormone deficiency, pain therapy, and treatment afterchemotherapy. For instance, diabetic patients may require injections ofinsulin several times a-day. The insulin dosage regime required for adiabetic patient varies depending on a number of factors including, forinstance, the type of diabetes, the type of insulin administered, theactual severity of the condition, the lifestyle of the patient, theroutine and diet of the patient. Accordingly diabetic patients oftenneed to administer doses of insulin themselves, several times a day, andin places other than hospitals or medical centres.

A number of drug delivery devices have been developed to facilitate theself-administration of medicaments. These devices are generally in theform of a patch pump integrating a cartridge containing a drug to beadministered, a micropump for pumping a predetermined volume of the drugfrom the cartridge and a transcutaneous delivery system comprising aneedle actuation mechanism for transcutaneous insertion of a cannula fordelivering the drug to a patient.

Examples of needle actuation mechanisms for transcutaneous insertion ofa cannula are given in WO2008/024810 and U.S. Pat. No. 7,846,132. Themechanisms have separate biasing elements to effect the needle insertionmovement and the needle withdrawal movement, which may have an adverseimpact on the reliability of such mechanisms. Moreover, using a septumaccording to WO2008/024810 configured to be pierced to bring a reservoirof a drug delivery device in fluid communication with the cannulaincreases the risk of contamination and the difficulty of ensuringsterile conditions.

One example of a micropump developed to be easily integrated into apatch pump is given in EP2992916. This pump is adapted for continuousdelivery of a liquid medication such as insulin for treatments ofdiabetes and comprises a piston provided with a rack engaging a piniongear of a motor and is mounted to move back and forth inside a floatingpiston which remains fixed by frictional engagement with the internalsurface of the pump housing. The floating piston comprises a channelconfigured to bring in fluid communication the piston chamber with theinlet and outlet of the pump housing when the torque produced by themotor overcomes the frictional engagement of the floating piston. Adrawback of this system includes the non-optimal ratio between thepumped volume and the pump size. Also, the pumped volume is invariableand defined by the fixed piston stroke, whereby for certainapplications, it would be desirable to be able to vary the pumpedvolume.

An object of the invention, according to a first aspect, is to provide adrug delivery device with a transdermal delivery system that isreliable, safe and comfortable for a patient.

It would be advantageous to provide a transdermal delivery systemconfigured to work with a thin needle and cannula gauge.

It would be advantageous to provide a transdermal delivery system thatprovides safe fluid connection between a reservoir and a cannula.

It would be advantageous to provide a transdermal delivery system thatis cost-effective to manufacture.

It would be advantageous to provide a transdermal delivery system thatis easy to operate and use.

It would be advantageous to provide a transdermal delivery systemcompatible with the injection of both standard and high viscosity drugs.

An object of the invention, according to another aspect, is to provide apump system for medical applications that is reliable, versatile, andcompact.

It would be advantageous to provide a pump system that is cost-effectiveto manufacture.

It would be advantageous to provide a pump system that is accurate, inparticular for pumping small volumes.

It would be advantageous to provide a pump system with low energyconsumption.

It would be advantageous to provide a pump system that can be used fordifferent medical applications.

It would be advantageous to be able to pump liquids with differentproperties, in particular with different viscosities, and in varyingvolumes.

An object of the invention, according to a third aspect, is to provide adrug reconstitution device that is reliable, in particular that enablesa good reconstitution of a drug, in a compact configuration.

It would advantageous to provide a drug reconstitution device that isversatile, in particular that can be used for different medicalapplications or that is able to reconstitute liquids with differentproperties, in particular with different viscosities, and in varyingvolumes.

It would be advantageous to provide a drug reconstitution device that iscost-effective to manufacture.

It would be advantageous to provide a drug reconstitution device that iseasy to operate and use.

It would be advantageous to provide a drug reconstitution device that ispower efficient.

SUMMARY OF THE INVENTION

Objects of the invention are achieved by a transdermal delivery systemof a drug delivery device according to claim 1.

Disclosed herein, according to a first aspect of the invention, is adrug delivery device comprising a transdermal delivery system having aneedle actuation mechanism configured for transdermal insertion of acannula and a needle guiding element for guiding axial displacement of aneedle and a cannula. The needle actuation mechanism comprises a cammember having a cam housing and a spring housed inside the cam housingin order to impart rotational movement to the cam member relative to theneedle guiding element. The guiding element guides a needle fixed to aneedle holder and a cannula fixed to a cannula holder. The needle andcannula holders comprise each an engagement portion, wherein theengagement portion of the needle holder is configured to engage with afirst and a second cam surface and the engagement portion of the cannulaholder is configured to engage with a locking surface. The first andsecond cam surfaces are arranged around the circumference of an outersurface of the cam housing along a first portion with a first gradientconfigured for the needle insertion movement followed by a secondportion with a second gradient configured for the needle retractionmovement such that the needle and the cannula are moved from a retractedposition to an extended position upon rotation of the cam member througha first predetermined angle, and such that the needle is brought back inthe retracted position upon further rotation of said cam member througha second predetermined angle, whereby during rotation through saidsecond predetermined angle, the engagement portion of the cannula holderabuts against the locking surface to maintain the cannula in theextended position.

In an embodiment, the first and second cam surface may advantageouslycorrespond to each side of a needle holder guide disposed around thecircumference of the cam member along a first gradient portionconfigured for the needle insertion movement followed by a secondgradient portion configured for the needle retraction movement.

The needle holder guide may for instance be a projecting part or agroove.

In an embodiment, the cam member may advantageously comprise a camhousing containing a spring element configured to impart angularmovement to the cam member so as to provide a self-driven cam member.

In an embodiment, in a position prior to use, the cam member may engagewith a cam engaging element to prevent rotation of the cam member.

The delivery system may advantageously further comprise a needleinsertion release mechanism configured to disengage the cam engagingelement to enable rotation of the cam member caused by the springelement.

In an embodiment, the needle guiding element comprises a needle housingfor sliding movement of the needle and cannula holders inside the needlehousing. A shape of the transversal cross-section of the housing maycorrespond to a shape of the transversal cross-section of the needle andcannula holders.

In an embodiment, the needle holder may advantageously be mounted on topof the cannula holder and cooperates with the needle guiding element toensure axial displacement of the needle and the cannula upon rotation ofthe cam member, wherein the cannula holder comprises a through hole forreceiving the needle.

In an embodiment, the cannula holder may comprise an inlet aperture forreceiving an inlet tube, and an inlet channel extending from the inletaperture to the through hole. The needle may advantageously be adaptedto perform the function of sealing between the inlet channel and thecannula to avoid any leakage prior to use of the delivery system.

In an embodiment, the inlet aperture of the cannula holder mayadvantageously be configured to be in fluid communication with thecannula once the needle is moved back in the retracted position afteractuation of the needle actuation mechanism of the transcutaneousdelivery system.

Also disclosed herein, according to a second aspect of the invention, isa drug delivery device including a transcutaneous delivery systemcomprising a needle actuation mechanism configured for transcutaneousinsertion of a needle, and a needle guiding element for axialdisplacement of a needle. The needle actuation mechanism comprises a cammember rotatable relative to the needle guiding element about an axisdistant from the needle axis. The cam member comprises a cam housingcontaining a biased element configured to impart angular movement to thecam member. The guiding element contains a needle connected to a needleholder. The needle holder comprises an engagement portion configured toengage with a first and a second cam surface of a needle holder guidedisposed around the circumference of the cam housing along a firstportion with a negative gradient followed by a second portion with apositive gradient such that the needle are moved between a retractedposition and an extended position upon rotation of the cam memberthrough a predetermined angle of rotation and such that the needle isbrought back in the retracted position upon further rotation of the cammember.

In an advantageous embodiment, rotation of the cam housing is stopped bya locking element when the needle has reached the extended position.Upon completion of the drug injection, a needle insertion releasemechanism disengages the locking element from the cam housing to enablefurther rotation of the cam housing to safely move the needle in theretracted position, thereby avoiding needle injury.

Objects of the invention are achieved by a pump system of a drugdelivery device according to embodiments described herein.

Disclosed herein, according to a third aspect of the invention, is apump system for a drug delivery device, comprising a pump drive and apump. The pump comprises a pump housing having inlet and outlet portsand forming a pump chamber containing a pump piston and a valve piston.The pump comprises a valve channel configured to selectively connect anddisconnect at least one of the inlet and outlet ports of the pumphousing to the pump chamber as a function of the position of the valvepiston. The pump piston and the valve piston are linearly slidable alonga common axis (A) within the pump chamber, and wherein the valve pistonand pump piston are independently actuated.

In an advantageous embodiment, the pump drive comprises a valve motorcoupled to the valve piston and a piston motor coupled to the pumppiston, the valve and piston motors being independently controllable.

In an embodiment, the pump drive comprises a first transmission couplingthe valve motor to the valve piston, and a second transmission couplingthe pump motor to the pump piston.

In an advantageous embodiment, each of the first and secondtransmissions comprises a toothed rack fixed to the respective piston,and a reduction gear assembly between the respective motor and toothedrack.

The pump drive may be configured to linearly actuate the valve pistonwithout any angular movement.

In an embodiment, the valve piston may be a single piece sealinglyfitted inside the pump housing. The valve channel may be configured toextend from the inner surface of the pump housing, through the valvepiston, into the pump chamber of the pump.

In an advantageous embodiment, the pump system the valve pistoncomprises an over-molded part comprising a valve channel portionconfigured to engage the inner surface of the pump housing so as to formwith said inner surface the valve channel.

In an advantageous embodiment, the over-molded part is configured toselectively seal the inlet and outlet ports from the pump chamber.

Also disclosed herein, according to a fourth aspect of the invention, isa drug reconstitution device including a pump system as described aboveaccording to the third aspect, whereby the pump housing comprises anadditional port, the additional port and the inlet port corresponding tofirst and second drug reconstitution ports. The drug reconstitutiondevice is configured for coupling a first constituent containercontaining a first constituent and a second constituent containercontaining a second constituent, wherein the outlet port of the pumphousing is configured to deliver the reconstituted drug comprising thefirst and second constituents.

In an advantageous embodiment, the drug reconstitution device furthercomprises a docking interface comprising a first and a second containerdocking interface configured to interconnect the first and secondconstituent containers respectively with the first and second drugreconstitution ports of the pump housing in a fluidic manner.

In an advantageous embodiment, the over-molded part of the valve pistonis configured to selectively seal the first and second drugreconstitution ports and the outlet port from the pump chamber.

In an advantageous embodiment, the valve piston of the pump of the drugreconstitution device may be formed in a single piece with overmoldedsealing parts such that the valve piston is sealingly fitted inside thepump housing.

In an advantageous embodiment, the valve channel of the valve piston ofthe pump of the drug reconstitution device may be configured to extendfrom the inner surface of the pump housing, through the valve piston,into the pump chamber.

Also disclosed herein, according to a fifth aspect of the invention, isa method for reconstituting a drug using a pump system comprising a pumpdrive and a pump having a pump housing comprising first and second drugreconstitution ports and an outlet port. The pump housing forms a pumpchamber containing a pump piston and a valve piston, wherein the pumpcomprises a valve channel configured to selectively connect anddisconnect at least one of the first and second reconstitution ports tothe pump chamber as a function of the position of the valve piston andwherein the pump piston and the valve piston are linearly slidable alonga pump axis (A) within the pump chamber, and wherein the valve pistonand pump piston are independently actuated.

The method may comprise the following steps: i.) setting the valvepiston in a first axial position in which the drug reconstitution portsof the pump housing are in fluid communication; ii.) urging a firstconstituent contained in a first container through the valve channel ofthe pump into a second container containing substance second constituentin order to reconstitute the drug inside the second container during adrug reconstitution phase; iii.) driving the pump piston away from thevalve piston along the pump axis to draw the reconstituted drug from thesecond container into the pump chamber during a chamber filling phase;iv.) driving the valve piston in a second axial position, uponcompletion of the chamber filling phase, in which the valve channel isaligned with the outlet port while the drug reconstitution ports areclosed by the valve piston; and v.) driving the pump piston towards thepiston valve along the pump axis to expel the reconstituted drug fromthe pump chamber, through the valve channel and the outlet port during adrug administration phase.

In an embodiment, the diluent or solvent contained in the firstcontainer is urged through successively the first drug reconstitutionport, the valve channel, the pump chamber, and the second drugreconstitution port into the second container during the drugreconstitution phase.

In an embodiment, the diluent or solvent contained in the firstcontainer is urged through successively the second drug reconstitutionport, the pump chamber, the valve channel, and the first drugreconstitution port into the second container during the drugreconstitution phase.

In an advantageous embodiment, the valve piston may be set in a safetyposition, prior to step i.) in which the drug reconstitution ports andthe outlet port of the pump housing are closed by the valve piston.

In an embodiment, the first container may be pressurized thereby urgingthe solvent from the first container into the second container duringthe drug reconstitution phase without having the need to drive the pumpsystem.

In an embodiment, the first container is in the form of a syringe. Thesolvent may be urged from the syringe to the second container when theplunger of the syringe is pushed to empty the syringe during the drugreconstitution phase.

Also disclosed herein, according to a sixth aspect of the invention, isa patch pump comprising the drug delivery device according to the firstaspect of the invention, the pump system according to the third aspectof the invention or the drug reconstitution device according to thefourth aspect of the invention, a cartridge, a power source and acontrol system.

Various features herein may be combined with one or more of the aboveaspects to provide combinations other than those specificallyillustrated and described. Further objects and advantageous features ofthe invention will be apparent from the claims, from the detaileddescription, and annexed drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

For a better understanding of the invention, and to show how embodimentsof the same may be carried into effect, reference will now be made, byway of example, to the accompanying drawings in which:

FIG. 1 is a perspective view of a drug delivery device in the form of apatch pump according to an exemplary embodiment of the invention;

FIG. 2 is a perspective view of a portion of the patch pump of FIG. 1without cover showing inter alia a pump system, cartridge and powersource of the patch pump;

FIG. 3 is another perspective view of a portion of the patch pump ofFIG. 1 without cover;

FIG. 4a is a perspective view of a part of the patch pump of FIG. 2,with the pump system comprising a transdermal delivery system and a pumpshown in cross-section according to an embodiment of the invention;

FIG. 4b is a close-up view of the pump of FIG. 4a of the pump system;

FIGS. 5a to 5e are perspective cross-sectional views of a portion of apump system according to an embodiment of the invention, whereby FIGS.5a to 5e illustrate different steps of a pumping sequence according toan embodiment of the invention;

FIG. 6a , and FIGS. 6b to 6n , are perspective cross-sectional,respectively plan cross-sectional, views of a portion of a pump systemaccording to another embodiment of the invention for reconstitution of adrug, whereby FIGS. 6b to 6n illustrate different steps of a pumpingsequence for drug reconstitution according to an embodiment of theinvention;

FIGS. 7a to 7g are cross-sectional views of the portion of the pumpsystem illustrating different steps of a pumping sequence for drugreconstitution according to another embodiment of the invention;

FIG. 8 is a perspective view of a valve piston according to anotherembodiment of the invention;

FIGS. 9a to 9e are perspective partial cross-sectional views of a pumpsystem comprising the valve piston of FIG. 8, showing the valve pistonin different axial positions.

FIGS. 10a to 10c are perspective and partial cross-sectional views of atransdermal delivery system of a drug delivery device, according to anembodiment of the invention;

FIG. 10d is a cross-sectional view of the transdermal delivery system ofFIG. 10 c;

FIGS. 11a and 11b are cross-sectional views of a needle guiding elementrespectively in a position prior to use and during use according to anembodiment of the invention;

FIGS. 12a to 12e are cross-sectional views of the transdermal deliverysystem of FIGS. 10a to 10c showing different sequences for transdermallyinsertion of a cannula according to an embodiment of the invention, and

FIGS. 13a and 13b are perspective views of the pump and the transdermaldelivery system respectively before and after actuation of a needleinsertion release mechanism.

DETAILED DESCRIPTION OF EXEMPLARY EMBODIMENTS

Referring to the figures, in particular FIGS. 1-3, a drug deliverydevice in the form of a patch pump 2 according to an embodiment of theinvention, includes a patch pump housing comprising a cover portion 3and a base 5 defining a skin bonding surface 5 b, a cartridge 4containing a drug to be administered, a power source, for instance inthe form of a battery 6, a pump system comprising a pump 14 and a pumpdrive 16 coupled to the pump via a transmission 52, 54, a transdermaldelivery system 10 and a control system 12 (FIG. 3) configured inparticular to operate the pump drive 16 of the pump system and torelease the transdermal delivery system for transdermally insertion of acannula as it will be described subsequently. The cover portion 3comprises an activation button 3 c and a status display 3 d. The skinbonding surface 5 b of the base 5 may be provided with an adhesivelayer, per se known in the field, for bonding the patch pump to apatient's skin.

As best seen in FIGS. 4a to 5e , the pump 14 comprises a pump housing 22provided with inlet and outlet ports 32, 34, a pump chamber 24, areciprocated pump piston 26 and a valve piston 28 configured to bedriven along an axial direction A without any angular movement about thevalve axis. The valve piston 28 is sealingly and slidably mounted insidethe pump housing 22 and includes a valve channel 44 configured toconnect the inlet port 32 with the pump chamber 24 so as to draw fluidfrom the inlet port 32, through the valve channel 44 into the pumpchamber 24 during a chamber filling stroke of the pump piston 26, and toconnect the outlet port 34 with the pump chamber 24 so as to expel fluidfrom the pump chamber 24 through the outlet port 34 during a chamberemptying stroke of the pump piston 26. A shown in particular in FIGS. 5aand 5b , the valve channel 44 of the valve piston 28 comprises a firstportion 44 a extending from the lateral guide surface 25 of valve pistonadjacent the inner surface 23 of the pump housing 22, and a secondportion 44 b extending to a chamber side face 27 of the valve pistonfacing the pump chamber 24. Various valve channel shapes, sizes andpositions between the lateral guide surface 25 and chamber side surface27 of the valve piston 28 may be configured.

In the illustrated embodiment, the inlet port 32 is fluidicallyconnected to the cartridge 4 through a first liquid conduit, forinstance in the form of a tube 33, while the outlet port 34 is connectedto the transdermal delivery system 10 through a second liquid conduit,for instance in the form of a tube 35 (FIGS. 4a and 4b ) as will bediscussed in more detail hereinafter. However, it may be appreciatedthat the pump 14 may be used in other medical applications where theinlet and outlet ports 32, 34 are not necessarily in fluid communicationwith a cartridge and a transdermal delivery system as illustrated. Fluidsources of various configurations may be connected to the inlet port,and fluid delivery systems of various configurations may be connected tothe outlet port, while benefitting from the advantages of the pumpsystem according to embodiments of this invention.

The valve piston 28 comprises sealing 46 engaging the inner surface 23of the pump housing 22. The valve piston 28 and the pump piston 26 maybe produced by various molding and other manufacturing techniques. Forinstance, the sealings may be separately formed (e.g. O-rings) from thepistons and assembled thereto, or form an integral part of the pistons,for example manufactured by two component injection molding.

The pump piston 26 and the valve piston 28 are coupled via respectivefirst and second transmissions 52, 54 to the pump drive 16. In theillustrated exemplary embodiment, the transmissions comprise a first anda second toothed rack 40, 48 fixed to respectively the pump piston 26,and the valve piston 28, engaging a pinion gear 50, 42 of a reductiongear chain coupled to the pump drive 16.

Advantageously, as best seen in FIG. 2, the pump drive 16 comprises avalve motor 31 coupled via a first transmission 52 to the valve piston,and a piston motor 30 coupled to the pump piston 26 via a secondtransmission 54. The piston and the valve motors 30, 31 are configuredto drive the pump piston and the valve piston independently from eachother. Each motor has two phases and comprises a first coil 30 a, 31 aand a second coil 30 b, 31 b. According to this driving configuration,the volume to be pumped may advantageously be adjusted for delivering anaccurate volume of a drug according to a variable dose setting. This maybe particularly advantageous for instance for accurately completing abolus administration of a drug.

The pump drive 16 may be operated by the control system 12 in order toimpart an axial displacement of the valve piston 28 relative to the pumppiston 26 in order to vary the stroke length of the pump piston therebyadjusting the volume of the pump chamber as required.

Although, reduction gears and racks have been described for thetransmissions between the motors and the pistons, it will be appreciatedthat other forms of transmissions may be used according to otherembodiments of the invention to couple the drive motors to the pistons,including worm gears, belt drive transmissions and linear actuators,that are per se known drive and transmission systems.

Referring in particular to FIGS. 5a to 5e , a pumping cycle according toan embodiment of the invention is illustrated. At the beginning of apump chamber filling step, as best seen in FIG. 5a , the valve piston 28is adjacent the pump piston 26, with the pump chamber 24 at essentiallyzero volume. The valve channel 44 is aligned with the inlet port 32 ofthe pump housing 22 while the outlet port 34 is sealed by sealings 46 b,46 c located around the circumference of the valve piston 28. It may benoted, in a variant, that the sealing could also be shaped tocircumscribe the outlet 34 without encircling the valve piston.

In a pump chamber filling step, as best seen in FIG. 5b , the pumppiston 26 is driven away from the valve piston 28 which remains fixedinside the pump housing 22. Fluid is therefore drawn from the inlet port32 through the valve channel 44 into the pump chamber 24.

Upon completion of the piston chamber filling stroke, both pump piston26 and valve piston 28 are driven in the same axial direction, over thesame distance, as illustrated in FIG. 5c to open the outlet port 34 andclose the inlet port 32. This is done by moving the valve piston 28 awayfrom the outlet port 34 such that the outlet port is in fluidcommunication with the pump chamber, and moving the valve channel 44 outof alignment with the inlet port 32. Sealing 46 c between the valvepiston and pump chamber housing inner surface 23 prevents liquid in thepump chamber from communicating with the inlet channel.

The pump piston 26 is then moved towards the valve piston 28 to expelthe fluid from the pump chamber 24 through the outlet port 34 as shownin FIGS. 5d and 5e , during a drug administration phase.

When a new or subsequent pump cycle is needed, after the end of the pumpchamber emptying phase, the valve piston 28 and pump piston are drivenback to the fill start position as illustrated in FIG. 5 a.

Because the pump piston and the valve piston are moved in the samedirection prior to expulsion of the liquid from the pump chamber, andthen also in the same opposite direction when moving from the end ofexpulsion step to the beginning of a new filling step, any play(tolerances) in the transmissions between the respective pistons andmotors are taken up before the pump chamber filling and before the pumpchamber emptying, thus reducing an alteration of the pumped volume dueto possible back-lash occurring when driving the pump piston and thevalve piston. Also, the volume of liquid to be pumped may be varied byvarying the stroke of the pump piston 26. The pump has therefore theadvantage of delivering precise adjustable volumes of a drug in acompact and simple configuration. Moreover, the pump configurationaccording to the invention is well suited for applications that requirelow energy consumption. Also, the valve piston 28 may be adjusted inseveral axial safety positions (see in particular FIGS. 6e, 6l and 7d )in order to prevent any fluid communication between the pump chamber 24and any ports 32, 34 of the pump housing 22 during axial displacement ofthe valve piston 28. The valve piston 28 is further configured to allowfluid communication between the pump chamber 24 and only one port of thepump as a function of the axial position of the valve piston.

The driving configuration of this pump is also well suited for a drugreconstitution device according to another embodiment of the inventionas shown in FIGS. 6a to 6n . The structure of the pump 14 is similar tothe pump which has just been described. The inlet port of the pumphousing 22 is however replaced by two drug reconstitution ports. Morespecifically, the drug reconstitution device may comprise a pump asshown in particular in FIG. 6a comprising a pump housing 22 providedwith two drug reconstitution ports 32, 36 and an outlet port 34, and adocking interface (not shown) configured for coupling a first and asecond constituent container containing respectively a solvent ordiluent and an active substance which may be preferably in the form of alyophilized substance. The docking interface may comprise a first and asecond container docking interface configured to interconnect the firstand second constituent containers respectively with the first and seconddrug reconstitution ports 32, 36 of the pump 14 in a fluidic mannerthrough respectively a first and a second channel in order to dissolvethe lyophilized substance so as to reconstitute a drug inside the secondconstituent container in a suitable form to be pumped into the pumpchamber 24 and expelled through the outlet port 34 for administration toa patient.

In advantageous embodiment, the drug reconstitution device may replacethe cartridge 4 in the patch pump 2 with the outlet port 34 of the pumpconnected to the transdermal delivery system 10 through a liquidconduit, for instance in the form of a tube for administering thereconstituted drug to a patient. The drug reconstitution device ishowever not necessarily integrated into a patch pump and may for examplebe incorporated in any type of fluid delivery device according toembodiments of this invention. The reconstituted drug may also beadministered to a patient through an infusion tube connected to theoutlet port 34 of the pump while benefitting from the advantages of thepump system according to embodiments of this invention.

Referring now in particular to FIGS. 6b to 6n , a pumping cycle of thepump of the drug reconstitution device according to an embodiment of theinvention is illustrated. At the beginning of a pump chamber fillingstep, as illustrated in FIG. 6b the valve piston 28 is adjacent the pumppiston 26, with the pump chamber 24 at essentially zero volume. Thevalve channel 44 is aligned with the first drug reconstitution port 32of the pump while the second drug reconstitution port 36 and the outletport 34 are sealed by customized sealings located of the valve piston28.

In a pump chamber filling step, as best seen in FIG. 6c , the pumppiston 26 is driven away from the valve piston 28 which remains fixedinside the pump housing 22. Solvent or diluent is therefore drawn fromthe first container through successively the first channel of thedocking interface, the first drug reconstitution port 32, the valvechannel 44 into the pump chamber 24.

Upon completion of the piston chamber filling stroke (FIG. 6d ), bothpump piston 26 and valve piston 28 are driven in the same axialdirection, over the same distance, as illustrated in FIG. 6e in order toalign the valve channel 44 with the second drug reconstitution port 36(figure f) to bring the second container in fluid communication with thepump chamber 24 and to seal the first drug reconstitution port 32 andthe outlet port 34 by the sealings located on the valve piston 28.

The pump piston 26 is then moved towards the valve piston 28, as shownin FIG. 6g , to expel the fluid from the pump chamber 24 through thevalve channel 44, the second drug reconstitution port 36, the secondchannel of the docking interface into the second container to dissolvethe lyophilized drug inside the second container during a drugreconstitution phase.

Upon completion of the piston drug reconstitution stroke (figure h), thepump piston 26 is driven away from the valve piston 28 which remainsfixed inside the pump housing 22, as illustrated in FIG. 6i . Thereconstituted drug is therefore drawn from the second container throughthe second channel of the docking interface, the second drugreconstitution port 36, the valve channel 44 into the pump chamber 24during a chamber filling step.

Upon completion of the piston chamber filling stroke (FIG. 6j ), bothpump piston 26 and valve piston 28 are driven in the same axialdirection, over the same distance, as illustrated in FIG. 6k , to openthe outlet port 34 and close the second drug reconstitution port 36while the first reconstitution port 32 remains close (FIG. 6l ).

The pump piston 26 is then moved towards the valve piston 28 to expelthe reconstituted drug from the pump chamber 24 through the outlet port34 as shown in FIGS. 6m and 6n , during a drug administration phase.

In an advantageous embodiment, the pump is configured for automated drugreconstitution according to successive steps of a pumping sequence asshown in FIGS. 7a to 7g . The first and second drug reconstitution ports32, 36 of the pump housing 22 may for example be connected torespectively a first and a second container (not shown) containingrespectively a pressurized solvent or diluent and an active substancewhich may be in the form of a lyophilized drug. During a drugreconstitution phase, as illustrated in FIG. 7a , the valve piston 28 isadjacent the pump piston 26. The valve channel 44 of the valve piston 28is aligned with the first drug reconstitution port 32 of the pump andthe second drug reconstitution port 36 is in fluid communication withthe second container such that the pressurized solvent or diluent isurged from the first container successively through the firstreconstitution port 32, the valve channel 44, the pump chamber 24, andthe second drug reconstitution port 36 into the second container inwhich the diluent dissolves the active substance to reconstitute a druginside the second container in a suitable form to be administered to apatient.

In a pump chamber filling step, as illustrated in FIG. 7b , the pumppiston 26 is driven away from the valve piston 28 which remains fixedinside the pump housing 22. The reconstituted drug is drawn from thesecond container through the second drug reconstitution port 36 into thepump chamber 24. The pump chamber filling step is preferably initiatedafter the whole content of the first container has been emptied so thatno more solvent is drawn into the pump chamber in the course of thisstep. An anti-backflow valve may however be mounted on the first drugreconstitution port 32 for safety reasons.

Upon completion of the piston chamber filling stroke (FIG. 7c ), bothpump piston 26 and valve piston 28 are driven in the same axialdirection, over the same distance, as illustrated in FIG. 7d , in orderto align the valve channel 44 with the outlet port 34 (FIG. 7e ) and toclose the first and second drug reconstitution ports 32, 36 by thesealings located on the valve piston 28.

The pump piston 26 is then moved towards the valve piston 28 to expelthe reconstituted drug from the pump chamber 24 through the valvechannel 44 and the outlet port 34 as shown in FIGS. 7f and 7g , during adrug administration phase

The pump system configuration advantageously requires only two strokesof the pump piston according to the above described sequence of a drugreconstitution process, thereby allowing fast drug reconstitution withlow power consumption.

In a variant, the solvent/diluent may be injected by a syringe bypiercing a septum arranged in the inlet port and pushing the plunger ofthe syringe to urge the solvent/diluent into the second container,whereupon the valve system is operated as described above.

In an advantageous embodiment as illustrated in FIG. 8, the valve piston28 comprises an over-molded part 49 over a portion of an outer surfaceof a valve piston core 28 a. The over-molded part 49 comprises sealingbeads configured to engage the inner surface 23 of the pump housing 22(FIG. 9a ) so as to form the valve channel 44 configured to selectivelyconnect and disconnect ports 32, 34 to the pump chamber 24 of a pumpsuitable for a drug reconstitution device or for delivery of drugs frommultiple drug containers. The valve channel 44 extends from the pumpchamber 24 to ports 32, 34 depending on the axial position of the valvepiston.

More particularly, the over-molded part 49 comprises a valve channelportion 49 a, 49 b which is surrounded by a sealing bead that engagesthe inner surface 23 of the pump housing 22 in order to form the valvechannel 44. The valve channel portion 49 a, 49 b comprises a valverecess 49 a and a valve groove 49 b in fluid communication with thevalve recess 49 a and the pump chamber 24. The valve recess 49 a extendscircumferentially over a certain angular distance in order to be influid communication with port 32 or port 34 of the pump as a function ofthe axial position of the valve piston 28. The over-molded part 49comprises additional recesses 49 c, 49 d, 49 e, 49 f surrounded bysealing beads arranged around the valve channel portion 49 a, 49 whichadvantageously selectively seals at least two ports according to thepumping sequence of the pump with a minimum of friction between theinner surface 23 of the pump housing 22 and the over-molded part 49,when the latter is actuated in translation.

The over-molded part 49 of the valve piston 28 may be made from a softcomponent such as a thermoplastic elastomer (TPE) or a silicon rubber inorder to achieve the function of sealing between port 32, port 34, port36 and the valve channel which is in fluid communication with the pumpchamber 24. The valve piston 28 according to this embodimentadvantageously reduces the number of components in contact with thepumped fluid, since the valve channel and the sealing are made from thesame material, thereby reducing the risk of generating particles withinthe pump. It also facilitates achieving conformity with drugcompatibility by reducing the number of materials to be tested.Moreover, the dimension tolerance of the valve piston core 28 a may beincreased without adverse effect on the sealing properties of the pumpthereby easing the production process.

As illustrated in FIG. 9a , the pump chamber 24 is sealed from both port32 and port 34 by the over-molded part 49 and is in fluid communicationwith port 36. Fluid may therefore be pumped from port 36 directly intothe pump chamber 24 or expelled from the pump chamber 24 through port 36depending on the pumping sequence and the pump configuration.

Axial displacement of the valve piston 28 towards the pump piston (notshown) brings the pump in a safety configuration in which all the ports32, 34, 36 are sealed from the pump chamber 24 by respective sealingrings surrounding (forming) the recesses 49 d, 49 f and 49 c of theover-molded part 49 (FIG. 8) as illustrated in FIG. 9 b.

Further axial displacement of the valve piston 28 towards the pumppiston (not shown) brings port 32 in fluid communication with the pumpchamber 24 through the valve channel portion 49 a, 49 b, whereby theother ports 34, 36 are sealed from the pump chamber 24 by sealing ringssurrounding forming the recesses 49 f and 49 c of the over-molded part49 as illustrated in FIG. 9c . Fluid may therefore be pumped from port32 through the valve channel (not shown) and into the pump chamber 24 orexpelled from the pump chamber 24 through the valve channel and port 32depending on the pumping sequence and the pump configuration.

Even further axial displacement of the valve piston 28 towards the pumppiston (not shown) brings the pump first in a safety configuration (FIG.9d ) in which all the ports 32, 34, 36 are sealed from the pump chamber24 by respective sealing rings surrounding the recesses 49 e, 49 f and49 d of the over-molded part 49 and then in a configuration (FIG. 9e )in which port 34 is in fluid communication with the pump chamber 24through the valve channel portion 49 a, 49 b, whereby ports 32, 36 aresealed from the pump chamber 24 by respective sealing rings aroundrecesses 49 e and 49 d of the over-molded part 49.

Any of ports 32, 34, 36 of the pump may function as an inlet port or anoutlet port according to the configuration of the pump. There may alsobe provided a greater plurality of ports, for instance four, five, sixor more ports. Ports may be connected to constituents of a drug to bereconstituted, for instance a powdered drug and a solvent, or to two ormore liquid drugs, or to a combination of drug constituents forreconstitution and liquid drugs. Multi drug therapy can thus beadministered by drawing in a liquid drug in the pump chamber from afirst port connected to a first drug recipient, moving the valve pistonto align the valve channel 44, 49 a, 49 b with an outlet port 34 andexpelling the first drug, then repeating the operation with a seconddrug in a second container connected to a second inlet port, forsequential delivery of drugs. Further drugs can be connected to third ormore ports and be delivered in a similar manner. It may also be possibleto mix two or more drugs in the pump chamber by sequential drawing in ofthe two or more drugs, the valve piston being moved between intakestrokes of the pump piston from one port connected to a first drug toanother port connected to another drug, before then moving the valvepiston to the outlet port for the expel phase.

The connection of two or more drug containers to respective two or moreinlet ports may also serve to provide an increased volume of medicamentin the medical device. For instance patient's with greater body weightmay require higher volumes of a drug in a delivery device, which may beprovided by connecting more than one drug container to the drug deliverydevice.

In an embodiment, the over-molded part 49 may be modified to perform thefunction of sealing between the inlet/outlet ports and the valve channelfor a pump of the type illustrated in FIGS. 5a to 5 e.

Referring now to FIGS. 10a to 10d , the transdermal delivery system 10according to another embodiment of the invention, comprises a needleactuation mechanism and a needle guiding element 20 for axialdisplacement of a needle and a cannula. The needle actuation mechanismcomprises a cam member 56 rotatable relative to the needle guidingelement 20. The cam member 56 has a cam housing 58, which may forinstance be generally cylindrical, and which comprises a bearing shaftreceiving portion 66 for rotation of the cam member 56 around a bearingshaft 67 and an annular compartment 68 lodging a biased element 60preferably in the form of a preloaded torsion spring configured toimpart rotational movement to the cam member 56. The bearing shaft maybe fixed to a base and/or cover of the patch pump housing. Otherrotation guide configurations may however be implemented. For instance,the cam housing may comprise an integral shaft at axial ends thereofthat engage in bearing cavities formed in or fixed to a base and/orcover of the patch pump.

The cam member 56 comprises a cam locking portion 65, as illustrated inparticular in FIG. 10a , which may be in the form of a land portionprovided on the lower part of the cam housing 58 to engage a camengaging element to prevent rotation of the cam member prior to use ofthe patch pump 2. The cam engaging element may be in the form of a rod47, as shown in FIG. 13a , with one end thereof abutting against theland portion of the cam housing while the other end of the rod isconnected to the valve piston. A needle insertion release mechanism isoperated by the control system 12, upon actuation of the button 3 cprovided on the cover portion 3 of the patch pump 2, which drives thevalve motor 31 in order to move the valve piston 28 away from the camhousing thereby disengaging the rod 47 from the land portion 65 as shownin FIG. 13b . Other cam engaging configurations may however beenvisaged. The end of the rod 47 may for instance be lodged inside anaperture formed in the cam housing.

In a variant, the needle insertion release mechanism may be manuallyoperated. For instance, the cam engaging element may protrude from anorifice formed on the patch pump housing and may be mounted on a springto translate between a first axial position in which the came engagingelement block the rotation of the cam member and a second axial positionin which the came engaging element is disengaged from the cam member.

FIG. 12a shows the transdermal delivery system 10 prior to use. Theneedle 72 and the cannula 76 are in a retracted position. The guidingelement 20 is preferably in the form of a cylindrical housing 70 whichcontains a needle 72 and a cannula 76 connected respectively to acylindrical needle holder 74 mounted on top of a cylindrical cannulaholder 78. The needle holder 74 comprises engagement portions 82 a, 82b, preferably in the form of projecting parts extending perpendicularlyto the needle/cannula axis to engage with a first and a second camsurfaces 62 a, 62 b provided on each side of a needle holder guide 63,which is in the form of a protruding part, disposed around thecircumference of the cam housing 58 of the cam member 56. The cannulaholder 78 comprises a locking portion 84, for instance in the form of aprojection extending transversely to the needle/cannula axis, configuredto engage a complementary locking portion, for instance a lockingshoulder 64 provided on a lower part of the cam member 56 and disposedaround a part of the circumference of the cam housing 58.

The needle guide 63 and locking surface 64 are arranged around thecircumference of the cylindrical housing 58 of the cam member 56 suchthat the needle 72 and the cannula 76 are moved together between aretracted position and an extended position upon rotation of the cammember 56 through a predetermined angle and such that the needle 72 isbrought back in the retracted position upon further rotation of the cammember 56 while the locking portion 84 of the cannula holder 78 abutsagainst the locking surface 64 to maintain the cannula in the extendedposition. The axial insertion of the cannula 76 is therefore imparted bythe movement of the needle holder 74, driven by the needle guide, whichpushes the cannula holder 78 downwards during insertion of the needle72, whereupon the locking portion 84 of the cannula holder 78 abutsagainst the locking surface 64 to securely maintain the cannula 76 inthe extended position.

The needle holder guide 63 is preferably arranged around thecircumference of the cam housing 58 along a first portion with adownward insertion gradient followed by a second portion with an upwardretraction gradient as to form an inclined protruding part whichresembles an ellipse in order to impart to the needle 72 the abovedescribed movements. However, it will be appreciated that the needleholder guide 63 may follow a slightly different trajectory to achievethe same function. For example, the gradient of the first and secondportions of the inclined protruding part may be higher or lower in orderto control the velocity of insertion and/or velocity of retraction ofthe needle optimally as needed for the comfort of use and reliability oftransdermal cannula placement.

The needle actuation mechanism has the advantage to impart an axialinsertion and retraction movement to the needle 72 through a rotation ofthe cam housing 58 that may be less than 360°, or in a variant (notshown), more than 360°.

In a variant (not shown), the protruding part of the needle holder guide63 may be replaced by a corresponding groove, configured to receive aprojecting part of the needle holder in order to achieve the samefunction.

According to an alternative embodiment of the invention (not shown), thetransdermal delivery system is configured for insertion of a needlewithout the use of a cannula. In this alternative embodiment, rotationof the cam housing is stopped by a locking element when the needle hasreached the extended position. Upon completion of the drug injection,the needle insertion release mechanism is used to disengage the lockingelement from the cam housing to enable further rotation of the camhousing to safely move the needle in the retracted position therebyavoiding needle injury.

As best seen in FIGS. 11a and 12b , the cannula holder 78 comprises athrough-hole 88 for receiving the needle 72 and comprises an inletaperture 86 for receiving an inlet tube 35 corresponding to the secondconduit connected to the outlet port of the pump described above. Theneedle housing 70 of the needle guiding element 20 comprises a verticalgroove 80 (FIG. 10b ) for accommodating a part of the inlet tube 35 whenthe cannula holder 78 is moved along its axis. Advantageously, theneedle 72 performs the function of sealing so as to avoid any leakageprior to use of the patch pump. To this end, the cannula holder 78comprises an inlet channel 87 extending from the inlet aperture 86 tothe through-hole 88. Accordingly, the inlet aperture 86 of the cannulaholder 78 is configured to be in fluid communication with the cannula 76once the needle 72 is moved back in the retracted position (FIG. 10e )after actuation of the transdermal delivery system.

With reference to FIGS. 12a to 12e , the working principle of thetransdermal delivery system according to an embodiment of the inventionwill now be described.

FIG. 12a shows the transdermal delivery system 10 prior to use. Theneedle 72 and the cannula 76 are in a retracted position. Upon actuationof the needle insertion release mechanism, the cam housing 58 of the cammember 56 rotates in a spring biased direction (counterclockwise in theillustration of FIG. 12b ) thereby imparting a downward movement to theneedle holder 74 and the cannula holder 78 in order to move the needle72 and the cannula 76 in the extended position.

FIG. 12c shows the transdermal delivery system 10 when both the needle72 and the cannula 76 are transdermally inserted after a rotation ofapproximately 180° of the cam housing 58. It may be noted that theneedle holder guide 63 may be configured with a different profile suchthat full needle insertion is achieved with a rotation of less than180°, or conversely with a rotation of more than 180°. In a variant, theneedle holder guide at its end of travel section may spiral above thestart position to allow the cam housing to rotate around more than 360°.

FIG. 12d shows the transdermal delivery system 10 after further rotationof the cam housing 58 in which the locking portion 84 of the cannulaholder 78 abuts against the locking surface 64 thereby securing thecannula 76 in the extended position. Further rotation of the cam housing58 moves the needle holder 74 engaging with needle holder guide 63upwards in order to bring the needle 72 in the retracted position,whereupon the inlet tube 35 is no longer sealed allowing the injectionof a drug as shown in FIGS. 11b and 12 e.

The above described transdermal delivery system is configured to workwith a needle diameter of 0.2 mm and a cannula diameter of 0.4 mm forthe injection of standard viscosity drug (up to 10 cST) thereby reducingpatient's discomfort.

For applications requiring high viscous drugs, the transdermal deliverysystem can be adapted with a higher fluid path diameter in order toallow the injection with low pressure losses between the pump and theend of the needle.

While this invention has been described with reference to severalembodiments, it should be appreciated that some changes may be broughtto the invention without departing from the scope of the invention. Forinstance, the arrangement of the inlet port, the outlet port and, ifapplicable, the drug reconstitution port(s) of the pump, as illustratedaccording to several embodiments of the invention, may be interchangedand/or the flow direction may be reversed according to the application.

LIST OF REFERENCED FEATURES

Drug delivery device

Patch pump 2

-   -   Patch Pump Housing        -   Cover 3            -   Activation button 3 c            -   Status display 3 d        -   Base 5            -   Skin bonding surface 5 b    -   Drug cartridge 4    -   Power source (battery) 6    -   Pump system        -   Pump 14            -   Pump housing 22                -   housing inner surface 23                -   Ports 32, 34, 36                -    Inlet/first drug reconstitution port 32                -   outlet port 34                -   second drug reconstitution port 36                -   inner surface 23            -   Pump chamber 24            -   Pump piston 26                -   Sealing 38                -    O-Ring            -   Valve piston 28                -   Valve piston core 28 a                -   lateral guide surface 25                -   chamber side face 27                -   Valve channel 44                -    first portion 44 a                -    second portion 44 b                -   Sealing 46, 46 a, 46 b, 46 c                -   Over-molded part 49                -    Valve channel portions 49 a, 49 b                -    Valve recess 49 a                -    Valve groove 49 b                -    Recesses 49 c, 49 d, 49 e, 49 f            -   first c0.onduit 33            -   second conduit 35        -   Pump drive 16            -   Piston motor 30                -   Two coils 30 a, 30 b            -   Valve motor 31                -   Two coils 31 a, 31 b        -   Transmission 52, 54            -   Toothed rack 40, 48            -   reduction gear train 53                -   pinion 42, 50            -   cam engaging element 47                -   Rod    -   Transdermal delivery system 10        -   Needle/Cannula Actuation Mechanism            -   Cam member 56                -   Cam housing 58                -    Cylindrical Housing                -    Shaft receiving portion 66                -    Bearing shaft 67                -    Annular compartment 68                -    Biased element 60                -    Preloaded Torsion Spring                -   Needle cam surfaces 62 a, 62 b                -    Needle holder guide 63                -   Cannula locking surface 64            -   Needle insertion release mechanism 65                -   Cam Locking Portion        -   Needle/cannula guiding element 20            -   Needle housing 70                -   Vertical groove 80        -   Needle 72            -   Needle holder 74                -   Cam Engaging Portions                -    Projecting parts 82 a, 82 b        -   Cannula 76            -   Cannula holder 78                -   Cam engaging portion 84                -   Inlet aperture 86                -   Inlet channel 87                -   Needle receiving means 88                -    Through Hole            -   Inlet tube 35    -   Control system 12        -   Electronic circuit board 90

The invention claimed is:
 1. A drug delivery device comprising: atransdermal delivery system having a needle actuation mechanism and aneedle assembly comprising: a needle connected to a needle holder, acannula connected to a cannula holder, and a needle guiding elementconfigured to guide axial displacement of the needle and the cannula,the needle actuation mechanism comprising: a cam member having a camhousing and a spring housed inside the cam housing in order to impartrotational movement to the cam member relative to the needle guidingelement, said needle and cannula holders comprising each an engagementportion, wherein the engagement portion of the needle holder isconfigured to engage with a first and a second cam surface and theengagement portion of the cannula holder is configured to engage with alocking surface, the first and second cam surfaces being arranged arounda circumference of an outer surface of the cam housing along a firstportion with a first gradient configured for a needle insertion movementfollowed by a second portion with a second gradient configured for aneedle retraction movement such that the needle and the cannula aremoved from a retracted position to an extended position upon rotation ofthe cam member through a first predetermined angle, and such that theneedle is brought back in the retracted position upon further rotationof said cam member through a second predetermined angle, whereby duringrotation through said second predetermined angle, the engagement portionof the cannula holder abuts against the locking surface to maintain thecannula in the extended position configured for transdermal delivery. 2.The drug delivery device according to claim 1, wherein said first andsecond cam surfaces correspond to each side of a needle holder guidedisposed around said circumference of the outer surface of the camhousing.
 3. The drug delivery device according to claim 2, wherein theneedle holder guide is a projecting part or a groove.
 4. The drugdelivery device according to claim 1, wherein in a position prior touse, the cam member is engaged with a cam engaging element to preventrotation of the cam member, said delivery system further comprising aneedle insertion release mechanism configured to disengage the camengaging element to enable rotation of the cam member caused by thespring.
 5. The drug delivery device according to claim 1, wherein theneedle guiding element comprises a needle housing for sliding movementof the needle and cannula holders inside the needle housing, wherein ashape of a transversal cross-section of the needle housing correspondsto a shape of a transversal cross-section of the needle and cannulaholders.
 6. The drug delivery device according to claim 1, wherein theneedle holder is mounted on top of the cannula holder and cooperateswith the needle guiding element to ensure axial displacement of theneedle and the cannula upon rotation of the cam member, wherein thecannula holder comprises a through hole for receiving the needle.
 7. Thedrug delivery device according to claim 6, wherein the cannula holdercomprises an inlet aperture for receiving an inlet tube, and an inletchannel extending from the inlet aperture to said through hole, theneedle being adapted to perform a function of sealing between the inletchannel and the cannula to avoid any leakage prior to use of thedelivery system.
 8. The drug delivery device according to claim 7,wherein the inlet aperture of the cannula holder is configured to be influid communication with the cannula once the needle is moved back inthe retracted position after actuation of the needle actuation mechanismof the transdermal delivery system.